Adenosine A3 receptor-mediated potentiation of mucociliary transport and epithelial ciliary motility
To examine the effect of adenosine A3 receptor stimulation on airway mucociliary clearance, we measured transport of Evans blue dye in rabbit trachea in vivo and ciliary motility of epithelium by the photoelectric method in vitro. Mucociliary transport was enhanced dose dependently by the selective A3 agonist N 6-(3-iodobenzyl)-5′- N-methylcarbamoyladenosine (IB-MECA) and to a lesser extent by the less-selective N 6-2-(4-amino-3-iodophenyl)ethyladenosine, whereas the A1 agonist N-cyclopentyladenosine (CPA) and the A2 agonist CGS-21680 had no effect. The effect of IB-MECA was abolished by pretreatment with the selective A3 antagonist MRS-1220 but not by the A1 antagonist 1,3-dipropyly-8-cyclopentylxanthine or the A2 antagonist 3,7-dimethyl-l-propargylxanthine. Epithelial ciliary beat frequency was increased by IB-MECA in a concentration-dependent manner, the maximal increase being 33%, and this effect was inhibited by MRS-1220. The IB-MECA-induced ciliary stimulation was not altered by the Rp diastereomer of cAMP but was greatly inhibited by Ca2+-free medium containing BAPTA-AM. Incubation with IB-MECA increased intracellular Ca2+ contents. Therefore, A3 agonist enhances airway mucociliary clearance probably through Ca2+-mediated stimulation of ciliary motility of airway epithelium.